Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.1.21 (thymidine kinase)
7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have constructed a map of the genes encoded by a 23,000-nucleotide-pair region of herpes simplex virus type 1. This region, defined by the three adjacent EcoRI fragments N (map coordinates 0.298 to 0.315), F (0.315 to 0.421), and M (0.421 to 0.448), has previously been shown by genetic analysis to contain the genes for thymidine kinase, nucleocapsid protein p40, glycoprotein B, DNA-binding protein, and DNA polymerase. We report the identification and mapping of RNAs defining 13 viral genes encoded by the region 0.298 to 0.448. The transcriptional pattern shows families of overlapping messages, similar to those observed in other regions of the viral genome. We also isolated mutants representing four distinct complementation groups and physically mapped several of the mutations to regions within EcoRI fragment F by marker rescue. Mutations representing complementation groups 1-9 (glycoprotein B), 1-1 (DNA-binding protein), and 1-3 (DNA polymerase) were mapped to coordinates 0.361 to 0.368 to 0.411, and 0.411 to 0.421, respectively. A fourth previously undefined complementation group was mapped to the region between glycoprotein B and DNA-binding protein. Comparing the transcription mapping with marker rescue data suggests that the genes for glycoprotein B, DNA-binding protein, DNA polymerase, and nucleocapsid protein p40 are expressed as 3.3-, 4.2-, 4.3- or 4.2- or both, and 2.4-kilobase mRNAs, respectively.
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PMID:Transcriptional and genetic analyses of the herpes simplex virus type 1 genome: coordinates 0.29 to 0.45. 619 14

Mutants dl312, dl314, hr1, and hr3 with mutations in region E1A of adenovirus type 5 were defective for the induction of cell cycle abnormalities detectable by flow cytometry, cell DNA replication, thymidine kinase production, and chromosome aberrations and did not synthesize the viral DNA-binding protein (E2A) in rat cells. dl311, a leaky E1A mutant, induced cell cycle effects at high multiplicity in only one of three experiments, and synthesized the DNA-binding protein. hr7 (E1B) gave a wild-type response in all tests. dl313 was also positive in all tests, although it induced fewer polyploid cells than did wild-type virus, probably because of the leftward extension of the dl313 E1B deletion into E1A. sub315 and sub316, with mutations which also span the E1A-E1B border, synthesized DNA-binding protein, but caused no cell cycle alterations detectable by flow cytometry in rat or mouse cells. Although the participation of other viral early regions cannot be completely excluded, our results suggest that alteration of cell cycle progression is a direct effect of E1A unrelated to its control of other viral early regions, and may be the function of E1A in transformation.
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PMID:Adenovirus-induced alterations of the cell growth cycle: a requirement for expression of E1A but not of E1B. 682 12

Our studies provide evidence for the presence of cyclin D1 in an early G1 cycle-specific DNA binding complex Yi1. Previously we identified several complexes including Yi and E2F that at different times during G0 to S transition bind to three distinct DNA sequences (MT1, MT2, MT3) located in the mouse thymidine kinase upstream promoter. These various complexes contain DNA binding proteins (Sp1, E2F, p110, p60), cyclins A and E, cyclin-dependent kinase 2 (cdk2), and retinoblastoma-related proteins (pRB, p107). Here we report that Yi1 is different from the E2F complexes. Yi1 contains cyclin D1/cdk2 kinase as shown by using specific antibodies to cyclins, cdks and the Yi1 DNA-binding protein in gel retardation, western blotting, and immunoprecipitation assays. Yi1 binding is specific to a consensus sequence different from that of E2F.
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PMID:Cyclin D1/cdk2 kinase is present in a G1 phase-specific protein complex Yi1 that binds to the mouse thymidine kinase gene promoter. 781 Dec 75

We report the fortuitous isolation of cDNA clones encoding a novel zinc finger DNA-binding protein termed BZP. The protein encoded is 114 kDa and contains eight zinc finger motifs, seven of which are present in two clusters at opposite ends of the molecule. Both finger clusters bound to the 9-bp sequence AAAGGTGCA with apparent Kds of approximately 2.5 nM. Two of the finger motifs within the amino- and carboxy-terminal finger clusters share 63% amino acid identity. BZP inhibited transcription of the herpes simplex virus thymidine kinase promoter when copies of the 9-bp target motif were linked in cis, suggesting that it functions as a transcriptional repressor. BZP mRNA and immunoreactivity were detected in several established cell lines but were most abundant in hamster insulinoma (HIT) cells, the parental source of the cDNAs. In mouse tissues, BZP mRNA and immunoreactivity were identified in cells of the endocrine pancreas, anterior pituitary, and central nervous system. Interestingly, in HIT cells proliferating in culture, BZP immunoreactivity was predominately nuclear in location, whereas it was usually located in the cytoplasm in most neural and neuroendocrine tissues. Serum deprivation of HIT cells caused BZP immunoreactivity to become predominantly cytoplasmic in location and attenuated its inhibitory effect on transcription, thereby suggesting that the both the subcellular location and the function of this protein are modulated by factors in serum.
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PMID:BZP, a novel serum-responsive zinc finger protein that inhibits gene transcription. 793 95

The 230-kD bullous pemphigoid antigen is a hemidesmosomal protein of the cutaneous basement membrane zone. We have previously cloned overlapping cDNAs corresponding to the human 230-kD bullous pemphigoid antigen gene (BPAG1), located at the human chromosomal locus 6p11-12. Utilizing the cDNA clones, a genomic DNA lambda FIX II phage library was screened. Seven over-lapping genomic clones, spanning approximately 20 kb, were isolated. These clones were shown to contain the entire approximately 9-kb coding sequence of BPAG1, and it consisted of 22 separate exons which varied from 78 to 2,810 bp in size. Elucidation of 2.6 kb of 5'-flanking DNA was found to contain several putative transcriptional response elements, and development of promoter chloramphenicol acetyltransferase (CAT) reporter gene constructs allowed identification of putative cis-elements which confer keratinocyte-specific expression to the gene. In particular, a putative AP2-binding sequence (KRE2) in the position -(1,786-1778) was shown to be responsible for marked enhancement of the endogenous promoter, as well as of a heterologous thymidine kinase/CAT construct, activity in normal human keratinocytes. Normal human keratinocyte nuclear extracts contained a protein, designated as KTP1, which complexed with the KRE2 oligomer by gel mobility shift assays. UV cross-linking and Southwestern analysis suggested that KTP1 is a DNA-binding protein clearly distinct from AP2, and this protein may be responsible for the basal keratinocyte-specific expression of the BPAG1 gene.
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PMID:Molecular biology of the 230-kD bullous pemphigoid antigen. Cloning of the BPAG1 gene and its tissue-specific expression. 804 59

We have recently cloned and characterized the entire human 230-kDa bullous pemphigoid antigen gene, which is expressed at a relatively high level in the basal keratinocytes. A putative AP2 binding sequence (KRE2), identified in the position -1786 to -1778, was cloned in front of a heterologous thymidine kinase chloramphenicol acetyltransferase construct, and transient transfections of normal human keratinocytes indicated a marked enhancement of the promoter activity. Normal human keratinocyte nuclear extracts contained a protein, designated as keratinocyte transcriptional protein-1 (KTP-1), which complexed with the KRE2 oligomer when examined by gel mobility shift assays. This protein was not detected in human skin fibroblast or HeLa cell nuclear extracts that did, however, contain AP2. UV cross-linking studies and Southwestern analyses suggested that KTP-1 binds to DNA as a single polypeptide of approximately 110 kDa. These data suggest that KTP-1 is a DNA-binding protein clearly distinct from AP2, and this protein may be responsible for the basal keratinocyte-specific expression of the bullous pemphigoid antigen gene.
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PMID:Identification of a DNA-binding protein (keratinocyte transcriptional protein-1) recognizing a keratinocyte-specific regulatory element in the 230-kDa bullous pemphigoid antigen gene. 827 41

Varicella-zoster virus (VZV) open reading frame 4 (ORF4) encodes a protein with a predicted molecular weight of 51,540 presenting amino acid sequence homology with the immediate-early regulatory protein ICP27 of herpes simplex virus type 1. To investigate the regulatory properties of the ORF4 gene product, we performed a series of transient expression assays in Vero cells, using a plasmid expressing ORF4 as effector and several VZV genes and heterologous genes as targets. The VZV target plasmids contained promoter/regulatory regions from genes belonging to the three putative VZV kinetic classes fused to the chloramphenicol acetyltransferase (CAT) gene. The heterologous target plasmids consisted of promoter/regulatory regions of human cytomegalovirus, Rous sarcoma virus, and human immunodeficiency virus type 1 fused to the reporter gene. These experiments demonstrated that the ORF4 gene product activated expression of ORF62 in a dose-dependent fashion but had no effect on the expression of the three other putative immediate-early genes (ORF4, ORF61, and ORF63). When various amounts of ORF4 were transfected in the presence of early gene promoters, dose-dependent transactivation was evidenced with the thymidine kinase gene (ORF36) and the major DNA-binding protein gene (ORF29) promoters; interestingly, little activity was detected with the promoter of the DNA polymerase gene (ORF28). No activation of late gene expression, represented by the glycoprotein I and glycoprotein II genes, was seen even over a wide range of concentrations of input ORF4 plasmid. Expression of pCMVCAT, pRSVCAT, and pHIVCAT was also stimulated by the ORF4 gene product. CAT mRNA analysis showed that activation of VZV target promoters occurs at the transcriptional and/or posttranscriptional level.
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PMID:Characterization of the regulatory functions of varicella-zoster virus open reading frame 4 gene product. 838 35

The Herpesviridae comprise a large class of animal viruses of considerable public health importance. Of the Herpesviridae, replication of herpes simplex virustype-1 (HSV-1) has been the most extensively studied. The linear 152-kbp HSV-1 genome contains three origins of DNA replication and approximately 75 open-reading frames. Of these frames, seven encode proteins that are required for originspecific DNA replication. These proteins include a processive heterodimeric DNA polymerase, a single-strand DNA-binding protein, a heterotrimeric primosome with 5'-3' DNA helicase and primase activities, and an origin-binding protein with 3'-5' DNA helicase activity. HSV-1 also encodes a set of enzymes involved in nucleotide metabolism that are not required for viral replication in cultured cells. These enzymes include a deoxyuridine triphosphatase, a ribonucleotide reductase, a thymidine kinase, an alkaline endo-exonuclease, and a uracil-DNA glycosylase. Host enzymes, notably DNA polymerase alpha-primase, DNA ligase I, and topoisomerase II, are probably also required. Following circularization of the linear viral genome, DNA replication very likely proceeds in two phases: an initial phase of theta replication, initiated at one or more of the origins, followed by a rolling-circle mode of replication. The latter generates concatemers that are cleaved and packaged into infectious viral particles. The rolling-circle phase of HSV-1 DNA replication has been reconstituted in vitro by a complex containing several of the HSV-1 encoded DNA replication enzymes. Reconstitution of the theta phase has thus far eluded workers in the field and remains a challenge for the future.
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PMID:Herpes simplex virus DNA replication. 924 11

In order to investigate the regulatory mechanisms involved in the transcription of the human oxytocin receptor (OTR) gene in the human myometrium at term of pregnancy, we subjected the 5' flanking region of the gene to a differential EMSA (electrophoretic mobility shift assay) procedure. Comparing nuclear proteins from term myometrium, in which OTR gene transcription is massively up-regulated, with those from the non-pregnant myometrium, indicated a prominent DNA-protein complex using the former extract. The sequence of the protein binding site was determined within 20 bp (TCTGCCTTCATCCAGCC) and designated as uterine stimulator motif-1 (US-1). The concatemerized US-1 sequence exhibited enhancer activity using a minimal thymidine kinase promoter (tk-81) in transfected SKN cells. We partially purified US-1 binding protein from SKN cells using a resin bead affinity procedure. Binding activity could be concentrated, although the protein eluate still comprised more than 20 component polypeptides. The molecular weight of the principal protein-DNA complex was determined following UV crosslinking to be 70 kDa. In circumstances where a cell-line mimicking the pregnant uterus at term is not available, the differential EMSA strategy, comparing OTR DNA protein binding in up- and down-regulated tissues, provides a powerful tool to investigate OTR regulation in the uterus. However, the precise characterization and identity of the specific DNA-binding protein(s) and consequent experimental verification of regulatory mechanisms still require elucidation.
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PMID:Differential protein-DNA binding analysis identifies a novel enhancer element, US-1, involved in the upregulation of the oxytocin receptor gene in human myometrium at term. 1022 79

The aim of this study was to investigate Epstein-Barr virus (EBV)-related virus infection in pet dogs. The presence of antibodies to EBV antigens and EBV-related DNA was determined by Western blot analysis and PCR, respectively. Among 36 pet dogs examined for serum antibodies, 32 (88.9%) were positive for EBV-specific thymidine kinase, 15 (41.7%) for EBV-encoded DNA-binding protein and 10 (27.8%) for EBV-specific DNA polymerase. A BamHI W fragment sequence encoding part of the EBV nuclear antigen leader protein was detected by PCR in corresponding leukocyte DNA samples. Among 21 dogs tested, 15 (71.4%) were positive for the BamHI W fragment sequence. The specificity of the amplified DNA fragments was confirmed by DNA sequencing. Within the amplified region of the BamHI W fragment (241 bp), DNA sequences detected in 10 dogs had 99.2% (two nucleotide variations), 99.6% (one nucleotide variation) or 100% identity to that of EBV. Furthermore, an EBV-encoded RNA signal was detected by in situ hybridization in dog lymphocytes, as well as in bone-marrow sections, indicating a latent infection with EBV or an EBV-like virus. In conclusion, although the sample size was small, these results showed that a widespread EBV-related gammaherpesvirus could be detected in the peripheral blood and bone marrow of pet dogs. Although no evident zoonotic transmission was detected, further studies are imperative for disclosing the biological significance of this canine EBV-like virus, which may correlate with human disorders.
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PMID:Discovery of Epstein-Barr virus (EBV)-encoded RNA signal and EBV nuclear antigen leader protein DNA sequence in pet dogs. 1578 84


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